Evidence of the health effects of inorganic arsenic (InAs) comes from ecological or retrospective studies. The overall goal of this proposal is to assemble a large cohort of adults to prospectively examine the short-term and intermediate-term health effects of such exposure, with an initial focus on skin lesions, skin cancers, biomarkers of As toxicity, and mortality. The creation of this cohort will also facilitate Project #4 which will study pregnancy outcomes and children's health in the same families. Ultimately this cohort serves as the base for future studies of long-term health effects of InAs exposure. We propose to recruit an follow 10,000 married men and women from Sonargaon, Bangladesh who have been exposed to a wide range of InAs (from < 10 mug/L to > 1000 mug/L) in drinking water. Interview data, blood and urine samples will be collected by trained personnel at the baseline. Follow-up interviews with the subjects will be conducted in year 3 in year 5. Incidences of skin lesions and skin cancers will be ascertained through physical examination by the study physicians followed by histopathologic confirmation be the study pathologist. The proposed study will be the first to prospectively examine the full dose-response relationship between arsenic exposure and skin lesions and skin cancers using individuals measurement data. The study will also examine the biomarkers, urinary arsenic species and TGFalpha, in relation to arsenic exposure (cross-sectionally in the baseline cohort) and in relation to the risk of skin lesions and skin cancers (prospectively using a case-cohort design nested within the total cohort).